SynthesisJournal of diabetes2025

Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction: A Systematic Review and Meta-Analysis.

Yucheng Yang, Liyun He, Shumeng Han, Na Yang, Yiwen Liu, Xuechen Wang, Ziyi Li, Fan Ping, Lingling Xu, Wei Li and 2 more

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Journal of diabetes, 2025. The graph read 6 numbers from its abstract, feeding 1 cell of the map: it favours the comparator in 1. Cited by 36 papers, 1 of them a synthesis that pooled it.

6numbers the graph read from it
1cell of the map it votes in
36citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

← favours the treatmentfavours the comparator →
6.670 · no effect
Weight reductionGLP-1RAs vs placebo, in femalesfavours the comparator · t2d, obesityfeeds one cell of the map
Δ 1.690.78 to 2.61
The meta-analysis showed that females lost more weight than males (MD 1.04 kg [95% CIs 0.70-1.38]; MD 1.69% [95% CI 0.78-2.61]).
Weight reductionGLP-1RAs vs placebo, in femalesfavours the comparator · t2d, obesityfeeds one cell of the map
Δ 1.040.70 to 1.38
The meta-analysis showed that females lost more weight than males (MD 1.04 kg [95% CIs 0.70-1.38]; MD 1.69% [95% CI 0.78-2.61]).
Weight reductiondulaglutide vs placebo, in dulaglutidefavours the comparator · t2d, obesityfeeds one cell of the map
Δ 0.880.63 to 1.12
Dulaglutide (MD 0.88 kg [95% CIs 0.63-1.12]) and semaglutide (MD 1.04 kg [95% CIs 0.45-1.63]) showed statistically significant differences in weight reduction between males and females.
Weight reductionGLP-1RAs vs placebo, in indications for weight reductionfavours the comparator · t2d, obesityfeeds one cell of the map
Δ 4.211.75 to 6.67
Subgroup analysis demonstrated that indications for weight reduction increased the gender difference in weight reduction (MD 4.21 kg [95% CIs 1.75-6.67]).
Weight reductionGLP-1RAs vs placebo, in overallfavours the comparator · t2d, obesityfeeds one cell of the map
Δ 0.880.67 to 1.09
The pooled results of GLP-1RAs indicated similar results (MD 0.88 kg [95% CIs 0.67-1.09]).
Weight reductionsemaglutide vs placebo, in semaglutidefavours the comparator · t2d, obesityfeeds one cell of the map
Δ 1.040.45 to 1.63
Dulaglutide (MD 0.88 kg [95% CIs 0.63-1.12]) and semaglutide (MD 1.04 kg [95% CIs 0.45-1.63]) showed statistically significant differences in weight reduction between males and females.

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×body weight & composition

ContradictsOpen on the map →What to test next →

40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 favour the comparator.

Belief with this paper
0.90replicated · 64 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT012722193,731 enrolled · 2011
Δ -5.39-5.82 to -4.95
Δ -17.3-18.1 to -16.6
NCT017204463,297 enrolled · 2013
Δ -2.95-3.47 to -2.44
NCT035489351,961 enrolled · 2018
Δ -12.4-13.4 to -11.5
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT056467061,407 enrolled · 2023
Δ -14.8-16.2 to -13.4
NCT018365231,398 enrolled · 2013
Δ -4.90-5.65 to -4.16
NCT035527571,210 enrolled · 2018
Δ -6.21-7.28 to -5.15
NCT007344741,202 enrolled · 2008
Δ -1.50-2.08 to -0.92
Δ -10.4-11.2 to -9.50
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Observational
  19. Review
  20. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

12 authors.

Yucheng YangDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Liyun HeDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Shumeng HanDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Na YangDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yiwen LiuDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Xuechen WangDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Ziyi LiDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0002-5227-421X
Fan PingDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0001-7650-6612
Lingling XuDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Wei LiDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Huabing ZhangDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0001-6259-7584
Yuxiu LiDepartment of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0001-7500-0855

Funding

Beijing Municipal Natural Science Foundation M22014CAMS Innovation Fund for Medical Sciences 2021-1-12M-002CAMS Innovation Fund for Medical Sciences 2023-I2M-C&T-B-043National High Level Hospital Clinical Research Funding 2022-PUMCH-B-015National Natural Science Foundation of China 91846106
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

aimTo verify sex differences of GLP-1RAs for weight reduction.

methodsWe searched RCTs reporting weight change by sex from PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials registries. Meta-regression was performed to evaluate the association between weight reduction and sex differences. Subgroup analyses were stratified by individual GLP-1RA medications, dose, treatment duration, indication, type of control, background treatment, and baseline weight. The study protocol was registered (CRD42023480167).

resultsFourteen studies covering dulaglutide, exenatide, liraglutide, semaglutide, and retatrutide were included in this study. The meta-analysis showed that females lost more weight than males (MD 1.04 kg [95% CIs 0.70-1.38]; MD 1.69% [95% CI 0.78-2.61]). The pooled results of GLP-1RAs indicated similar results (MD 0.88 kg [95% CIs 0.67-1.09]). Meta-regression illustrated that substantial weight reduction was significantly relevant to greater gender differences (β = -0.19 [95% CIs -0.29 to -0.09]). Subgroup analysis demonstrated that indications for weight reduction increased the gender difference in weight reduction (MD 4.21 kg [95% CIs 1.75-6.67]). Background treatment, dose, duration of treatment, baseline weight, and type of control had no subgroup differences in the sex difference in weight reduction of GLP-1RAs. Dulaglutide (MD 0.88 kg [95% CIs 0.63-1.12]) and semaglutide (MD 1.04 kg [95% CIs 0.45-1.63]) showed statistically significant differences in weight reduction between males and females. No gender difference was observed in the exenatide subgroup analysis.

conclusionsFemales lost more weight than males when treated with GLP-1RAs for weight reduction. The sex difference in weight reduction became more pronounced as the degree of weight reduction increased. Indications for obesity could magnify this sex difference.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsObesityWeight LossExenatideFemaleGlucagon-Like Peptide 1Glucagon-Like PeptidesHumansImmunoglobulin Fc FragmentsMaleRecombinant Fusion ProteinsSemaglutideSex CharacteristicsSex FactorsdulaglutideExenatideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesHypoglycemic AgentsImmunoglobulin Fc FragmentsRecombinant Fusion ProteinsSemaglutide

Identifiers

PMID40040445
PMCPMC11880690

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.